112 research outputs found
Single nucleotide polymorphisms of HSP90AA1 gene influence response of SLE patients to glucocorticoids treatment
The effects of Ξ²-glucan on human immune and cancer cells
Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as Ξ²-glucans. Ξ²-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, Ξ²-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by Ξ²-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1β3 linear Ξ²-glycosidic chain of Ξ²-glucans cannot be digested. Most Ξ²-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small Ξ²-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, Ξ²-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate Ξ²-glucans is essential if we wish to investigate the effects of Ξ²-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified Ξ²-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of Ξ²-glucans or Ξ²-glucans containing compounds
Pseudomonas aeruginosa Eliminates Natural Killer Cells via Phagocytosis-Induced Apoptosis
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes the relapse of illness in immunocompromised patients, leading to prolonged hospitalization, increased medical expense, and death. In this report, we show that PA invades natural killer (NK) cells and induces phagocytosis-induced cell death (PICD) of lymphocytes. In vivo tumor metastasis was augmented by PA infection, with a significant reduction in NK cell number. Adoptive transfer of NK cells mitigated PA-induced metastasis. Internalization of PA into NK cells was observed by transmission electron microscopy. In addition, PA invaded NK cells via phosphoinositide 3-kinase (PI3K) activation, and the phagocytic event led to caspase 9-dependent apoptosis of NK cells. PA-mediated NK cell apoptosis was dependent on activation of mitogen-activated protein (MAP) kinase and the generation of reactive oxygen species (ROS). These data suggest that the phagocytosis of PA by NK cells is a critical event that affects the relapse of diseases in immunocompromised patients, such as those with cancer, and provides important insights into the interactions between PA and NK cells
Primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9β10:1) with a prevalence of up to 1 in 1,000 women over 40Β years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13β15Β mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC
A Review of Approaches Targeting the Replacement of Coccidiostat Application in Poultry Production
The position dependent 15N enrichment of nitrous oxide in the stratosphere
The position dependent "N fractionation of nitrous oxide (N20). which cannot be obtained from mass spectrometric analysis on molecular N20 itself, can be determined with high precision using isotope ratio mass spectrometry on the NO+ fragment that is formed on electron impact in the source of an isotope ratio mass spectrometer. Laboratory UV photolysis experiments show that strong position dependent 15N fractionations occur in the photolysis of N2O in the stratosphere, its major atmospheric sink. Measurements on the isotopic composition of stratospheric N20 indeed confirm the presence of strong isotope enrichments, in particular the difference in the fractionation constants for 15N'4N0 and ''N'5N0. The absolute magnitudes of the fractionation constants found in the stratosphere are much smaller, however, than those found in the lab experiments, demonstrating the importance of dyaamicai and also additional chemical processes like the reaction of N20 with WID)
Difference between blocking and nΓ©el temperatures in the exchange biased Fe\u3csub\u3e3\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e/CoO system
\u3cp\u3eThe blocking temperature T\u3csub\u3eB\u3c/sub\u3e has been determined as a function of the antiferromagnetic layer thickness in the Fe\u3csub\u3e3\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e/CoO exchange biased system. For CoO layers thinner than 50 Γ
, T\u3csub\u3eB\u3c/sub\u3e is reduced below the NΓ©el temperature T\u3csub\u3eN\u3c/sub\u3e of bulk CoO (291 K), independent of crystallographic orientation or film substrate (Ξ±-Al\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e, SrTiO\u3csub\u3e3\u3c/sub\u3e, and MgO). Neutron diffraction studies show that TB does not track the CoO ordering temperature and, hence, that this reduction in T\u3csub\u3eB\u3c/sub\u3e does not arise from finite-size scaling. Instead, the ordering temperature of the CoO layers is enhanced above the bulk TN for layer thicknesses β²100Γ
due to the proximity of magnetic Fe3O4 layers.\u3c/p\u3
Application of the MIDAS approach for analysis of lysine acetylation sites.
Multiple Reaction Monitoring Initiated Detection and Sequencing (MIDASβ’) is a mass spectrometry-based technique for the detection and characterization of specific post-translational modifications (Unwin et al. 4:1134-1144, 2005), for example acetylated lysine residues (Griffiths et al. 18:1423-1428, 2007). The MIDASβ’ technique has application for discovery and analysis of acetylation sites. It is a hypothesis-driven approach that requires a priori knowledge of the primary sequence of the target protein and a proteolytic digest of this protein. MIDAS essentially performs a targeted search for the presence of modified, for example acetylated, peptides. The detection is based on the combination of the predicted molecular weight (measured as mass-charge ratio) of the acetylated proteolytic peptide and a diagnostic fragment (product ion of m/z 126.1), which is generated by specific fragmentation of acetylated peptides during collision induced dissociation performed in tandem mass spectrometry (MS) analysis. Sequence information is subsequently obtained which enables acetylation site assignment. The technique of MIDAS was later trademarked by ABSciex for targeted protein analysis where an MRM scan is combined with full MS/MS product ion scan to enable sequence confirmation
The Effect of Submicron Second-Phase Particles on the Rate of Grain Refinement in a Copper-Oxygen Alloy During Cold Spray
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